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Journal of Chemistry
Volume 2013 (2013), Article ID 427181, 14 pages
Research Article

Molecular Modeling Studies of Substituted 2,4,5-Trisubstituted Triazolinones Aryl and Nonaryl Derivatives as Angiotensin II AT1 Receptor Antagonists

1Drug Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour University, Sagar 470 003, India
2Department of Chemistry, Chaudher Dilip Singh Kanya Mahavidyalaya, Bhind 477001, India

Received 26 June 2012; Revised 21 October 2012; Accepted 21 October 2012

Academic Editor: Tomokazu Yoshimura

Copyright © 2013 Mukesh C. Sharma et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The development of new therapies to treat hypertension and cardiovascular diseases. A series of 2,4,5-trisubstituted triazolinones aryl and nonaryl derivatives were subjected to Group-based QSAR, -nearest neighbour molecular field analysis, and pharmacophore mapping. Multiple linear regression (MLR) methodology coupled with feature selection method namely simulated annealing, was applied to derive Group based QSAR models which were further validated for statistical significance and predictive ability by internal and external validation. The best physicochemical descriptors, namely, R1chiV1, R2T_N_O_3, R2chlorines count, R2T_C_N_4, and R2SssNHE index, contribute significantly to the biological activity. The statistically significant best Group-based QSAR model has and with pred_. The 3D-QSAR studies were performed using the simulated annealing selection -nearest neighbor molecular field analysis approach; a leave-one-out cross-validated correlation coefficient and predicate activity pred_ were obtained. Contour maps using this approach showed that steric, electrostatic, and hydrophobic effects dominantly determine binding affinities. Pharmacophore hypotheses were generated by the mol sign module and found to contain common features like hydrogen bond donor acceptor, donor, positive, negative ionizable, and hydrophobic features. This model can be used for preliminary screening of large number of substituted 3H-1,-2,-4 triazolinone aryl and nonaryl derivatives. The information rendered by 3D-QSAR models may lead to a better understanding of structural requirements of triazolinone aryl and nonaryl derivatives and also aid in designing novel potent antihypertensive molecules.